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윤현호Hyunho Yoon

가톨릭대학교

J. Med. Virol., Dec 2023, 95 (12) | https://doi.org/10.1002/jmv.29309 mRNA-HPV vaccine encoding E6 and E7 improves therapeutic potential for HPV-mediated cancers via subcutaneous immunization

Seonghyun Lee ^1,2, Hyunho Yoon ^1,2, Seol Hee Hong^3,4, Sung Pil Kwon ⁵, Jung Joo Hong ^6,7, Hye Won Kwak ⁸, Hyeong-Jun Park ⁸, Soyeon Yoo ⁵, Seo-Hyeon Bae ^1,2, Hyo-Jung Park ^1,2, Jisun Lee¹, Yoo-Jin Bang ^1,8, Yu-Sun Lee ^1,2, Jae-Yong Kim ^1,8, Subin Yoon^1,2, Gahyun Roh ^1,2, Youngran Cho ^1,2, Yongkwan Kim⁸, Daegeun Kim⁸, Sang-In Park ⁸, Do-Hyung Kim ^1,8, Sowon Lee ¹, Ayoung Oh ^1,2, Dahyeon Ha ^1,2, Soo-Yeon Lee ^1,2, Misung Park ^1,2, Eun-Ha Hwang ⁶, Gyuseo Bae ⁶, Eunsu Jeon ⁶, Sung Hyun Park ⁶, Won Seok Choi ⁶, Ho Rim Oh⁹, In Woo Kim⁹, Hyewon Youn ^9,10, Gyochang Keum ⁵, Eun-Kyoung Bang ⁵, Joon Haeng Rhee ¹¹, Shee Eun Lee ^3,4, Jae-Hwan Nam^1,2

¹Department of Medical and Biological Sciences, The Catholic University of Korea, Bucheon, Gyeonggi-do, South Korea.

²BK21 four Department of Biotechnology, The Catholic University of Korea, Bucheon, Gyeonggi-do, South Korea.

³National Immunotherapy Innovation Center, Hwasun-gun, Jeonnam, South Korea.

⁴Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, South Korea.

⁵Brain Science Institute, Korea Institute of Science and Technology, Seoul, South Korea.

⁶National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, Chungcheongbuk-do, South Korea.

⁷KRIBB School of Bioscience, Korea University of Science & Technology (UST), Daejeon, South Korea.

⁸R&D Research Center, SML Biopharm, Gwangmyeong, Gyeonggi-do, South Korea.

⁹Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.

¹⁰Department of Nuclear Medicine, Cancer Imaging Center, Seoul National University Hospital, Seoul, South Korea.

¹¹Department of Microbiology, Chonnam National University Medical School, Hwasun-gun, Jeonnam, South Korea.

Seonghyun Lee, Hyunho Yoon, Seol Hee Hong, Sung Pil Kwon, and Jung Joo Hong contributed equally to this work.

CORRESPONDING AUTHORS : Shee Eun Lee, Jae-Hwan Nam

Abstract

The E6 and E7 proteins of specific subtypes of human papillomavirus (HPV), including HPV 16 and 18, are highly associated with cervical cancer as they modulate cell cycle regulation. The aim of this study was to investigate the potential antitumor effects of a messenger RNA-HPV therapeutic vaccine (mHTV) containing nononcogenic E6 and E7 proteins. To achieve this, C57BL/6j mice were injected with the vaccine via both intramuscular and subcutaneous routes, and the resulting effects were evaluated. mHTV immunization markedly induced robust T cell-mediated immune responses and significantly suppressed tumor growth in both subcutaneous and orthotopic tumor-implanted mouse model, with a significant infiltration of immune cells into tumor tissues. Tumor retransplantation at day 62 postprimary vaccination completely halted progression in all mHTV-treated mice. Furthermore, tumor expansion was significantly reduced upon TC-1 transplantation 160 days after the last immunization. Immunization of rhesus monkeys with mHTV elicited promising immune responses. The immunogenicity of mHTV in nonhuman primates provides strong evidence for clinical application against HPV-related cancers in humans. All data suggest that mHTV can be used as both a therapeutic and prophylactic vaccine.

논문정보

형식Research article
게재일2023년 12월 (BRIC 등록일 2023-12-19)
연구진국내 연구진
분야 생명과학 > 미생물학

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